Effects of pulsed ethanol consumption on mammary tumorigenesis in non-parous mice
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Ethanol has been implicated as the only dietary factor that increases the risk of breast cancer in women. It is not known whether the effects of ethanol exposure are the same throughout the lifetime, or if ethanol exerts a greater effect at times of rapid remodeling of breast tissue, such as puberty or post-lactational involution, compared to a resting adult state. The purpose of this study was to define the effects of short term pulsing with ethanol on subsequent tumor development and metastasis in resting, nonparous mice. These resting mice served as age-matched controls for a larger study comparing ethanol's effects on parous mice when administered during post-lactational involution. For this project, transgenic FVB-MMTV-HER2/neu mice, which overexpress the epidermal growth factor receptor type 2 in the mammary gland, were used to model the etiology of HER2-overexpressing human breast cancers. Nonparous female mice, aged 130-145 days, were administered 0, 0.5%, 1%, or 2% ethanol in liquid diets for a 2 week period, and then evaluated for tumorigenesis over the following 9 months. No significant difference was observed between control or ethanol-fed mice in terms of tumor latency, multiplicity, burden, or growth rate. Histopathology of tumors was unchanged by diet in terms of nuclear score, glandular differentiation or mitotic index, suggesting that the tumor grade remains unaffected by the pulsed ethanol dosing. Short pulsed ethanol consumption did not seem to have a significant effect on changes in erbB2, TGF-beta, COX-2 or aromatase expression levels. However, nonparous mice show an increased latency compared to parous mice, confirming that parity accelerates tumorigenesis in these mice which might be seen in part due to exposure of parous mice to increased progesterone levels. Ethanol feeding likewise has no effect on frequency of lung metastases. These results show that ethanol consumption for short time periods has no effect on Her-2-mediated mammary tumorigenesis in the nonparous mouse.